Health Comments

Assessing medical therapies without RCTs

2011-08-20T22:23:07Z

The July 2011 issue of Scientific American ran a rather interesting article on comparing the effectiveness of medical therapies (1). The piece, The Best medicine, is subtitled A quiet revolution in comparative effectiveness research just might save us from soaring medical costs. I doubt the savings in medical costs — every dollar spent on medical services is a dollar earned by someone providing those 'services', and those providers aren′t going to give up their slice of the pie without a fight. But I like the 'quiet revolution' in comparative effectiveness research (CER).

What′s so revolutionary about it? It doesn′t rely on randomized controlled trials (RCTs), the 'gold standard' that medical therapy is supposedly based on. Instead, investigators take advantage of the availablilty of detailed electronic medical records from millions of patients. Analyzing these data, researchers believe, yields results that are every bit as rigorous, at a fraction of the cost of RCTs.

RCTs are undoubtedly the best tool for the initial assessment of the safety and efficacy of new drugs. Randomly assigning study participants to either a treatment or a control group minimizes confounding differences; patients assigned by chance to either the treatment or the control groups are likely similar in all aspects except the therapy in question. Hiding these assignments from both patients and doctors (blinding) should minimize the placebo effect on the patient and bias on the part of the physician interpreting the 'treatment' results.

But once drugs are approved and prescribed, blinding and randomization become irrelevant. Therapies need to be assessed in real-world clinical settings where both doctors and patients know the treatment protocol. And detailed medical records contain all the relevant health, socioeconomic and other details for comparing patients known to be similar in every respect except the therapy in question.

The limitations of RCTs are well known (2), but they remain the 'gold standard' in medical research, the evidence to be given the greatest weight. Yet, much as Big Pharma would have us believe otherwise, most therapies aren′t supported by RCTs. The majority of drugs are prescribed for off-label use, and the majority of patients are taking drug combinations. Neither off-label use nor most drug combos are supported by RCTs. To quote one investigator, "There is a chasm between what gets done in practice and what science has shown" (1)

The insistence on RCT-based evidence as the ultimate authority is hypocritical and self-serving. It will undoubtedly be used to dismiss CER-based reassessments of existing therapies if those therapies are found to be ineffective. Insisting on RCT-backed evidence is also useful for discrediting 'alternative' therapies as 'unscientific'. Yet, RCTs are simply inappropriate in most areas of health and nutrition research. For example, it makes no sense to study supplementation with single nutrients in isolation; all nutrients are needed in the right amounts for optimal health.

Obviously we need, and should insist on, evidence-based therapies. But it is ridiculous to equate sound scientific evidence exclusively with randomized controlled trials. Let′s hope that this 'quiet revolution in comparative effectiveness research' takes a firm hold and relegates RCTs to the drug approval stage where they truly are the best strategy.

This new type of comparative effectiveness research may or may not alter medical practice and lower medical costs. But at least it should tell us, the patients, which of the available therapies are actually effective. If we are to be partners in making decisions that affect our health and wellbeing we need reliable information untainted by the financial interests of the medical/pharmaceutical establishment. By insisting on therapies that′ll actually do us some good we, the patients, might just help bring down medical costs.

Sources

Sharon Begley, The best medicine. A quiet revolution in comparative effectiveness research just might save us from soaring medical costs. Scientific American July 2011, 50-55.
Black N, Why we need observational studies to evaluate the effectiveness of health care. Br Med J 1996;312:1215.
http://www.bmj.com/content/312/7040/1215.full

Excess Calories, Weight Gain and Exercise

2011-07-25T21:51:06Z

As you know, we have a system of hormones that adjust our energy intakes — through hunger and satiety signals — to match our energy needs. What happens if we override this control system and overeat? Could it be that our bodies simply increase their energy expenditure to dispose of any excess calories? A couple of recent articles (1,2) make me think that this may indeed be the case.

The first study (1) examined the effects of changes in portion sizes, numbers of daily eating/drinking occasions, and food energy densities on weight gains in adult Americans between 1977-1978 and 2003-2006. The investigators found that daily energy intake increased by an astonishing 570 Kcal during that period. Americans ate more often and they ate larger portions; the energy density of their food, on the other hand, didn′t change much.

The second study (2) estimated the independent contributions of diet, exercise and other lifestyle factors to weight change. More than 120,000 healthy non-obese Americans were followed between 1986 and 2006, and changes in lifestyle and weight were assessed every four years. The investigators found average weight gains of 0.8 lb per year; the top 5% increased their weight by about 3 lb annually. Physical activity in the least and most active 20% surveyed shaved ½ lb and 2½ lb, respectively, off the overall weight gain.

Back to that increase in energy intake of 570 Kcal per day (1). It is actually about twice as high as the 1971 to 2004 increases reported by the American Heart Association (3). According to those estimates, women increased their average daily energy consumption by 344 Kcal (from 1542 to 1886) and men by 243 Kcal (from 2450 to 2693). Even those increases are still substantial. If we assume that Americans ate enough food in the seventies to meet all their daily energy needs then these 243 (or 344 or 570) Kcal have to be considered excess energy. What does the body do with this excess?

Could these extra calories simply be stored as fat? That′s highly unlikely. Suppose that every day you stored 10 Kcal as fat. In one year you would put away an extra 3,650 Kcal, about the energy content of one pound of fat (3,500 Kcal). In other words, for every 10 Kcal stored per day you gain 1 lb per year. If your energy intake increased by 243 Kcal per day (the lowest of the three estimates) you would gain about 25 lb per year; this is about an order of magnitude more than the top weight gain of 3 lb quoted in ref. 2.

An increase in physical activity doesn′t use up this excess energy either. Even the top 20% — the most active — of the participants in the second study only managed to burn about 2½ lb per year (2), or about 25 Kcal per day. Again, this is only about one tenth of the lowest estimated consumption increase.

Since neither fat storage nor increased physical activity — nor for that matter a combination of the two — accounts for that energy excess, what happens to those extra calories? I can only see two other possibilities. Either they simply 'pass through', i.e. the extra food is not digested and absorbed, or the body increases its energy expenditure to use up that excess.

Could energy expenditure really rise in response to increased energy availability? I′ve never come across any discussion on that topic, and the authors of the papers I quoted don′t talk about it either. But if this is correct then it isn′t surprising that diets don′t work — the energy requirements you try to match or beat are a moving target.

Sources:

Duffey KJ, Popkin BM, Energy density, portion size, and eating occasions: Contributions to increased energy intake in the United States, 1977-2006.PLoS Medicine 2011;8(6):e1001050.
http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001050
Mozaffarian D, Hao T, Rimm EB et al. Changes in diet and lifestyle and long-term weight gain in women and men. N Engl J Med 2011;364:2392-2404.
http://anpron.eu/wp-content/uploads/2011/06/Changes-in-Diet-and-Lifestyle-and-Long-Term-Weight-Gain-in-Women-and-Men.pdf
Lloyd-Jones D, Adams RJ, Brown TM et al. Executive summary: Heart disease and stoke statistics – 2010 update: A report from the American Heart Association. Circulation 2010;121(7):948-954.
http://circ.ahajournals.org/content/121/7/948.full.pdf

Are nutritional supplements a waste of money?

2011-05-26T22:30:23Z

Do we really need nutritional supplements — and would they even do us any good? If we believe the naysayers, nutritional supplements like vitamins and minerals are worthless; no clinical vitamin/mineral trial has ever shown any benefit. Besides, we′re told, we can get all our vitamins and minerals from a balanced diet.

Relying on our diets for all our nutritional needs is simply unrealistic. There might well be such a thing as a "complete balanced diet", but survey after survey has shown that hardly anyone follows dietary recommendations. If you get all your necessary nutrients from the food you eat you are truly an exception.

Yet, there are nutrients that we simply can′t do without. We need vitamins, minerals, essential fatty acids and essential amino acids because we either cannot make them at all or cannot make them in adequate amounts. If we don′t get them from food and drink — and every nutrition survey shows that we don′t — where else could get them but from supplements? So, how could supplementation be found to be useless?

The reason why nutrient trials usually give disappointing results is that they employ tools designed to evaluate pharmaceutical drugs. But nutrients aren′t drugs, and methods like randomized controlled trials (RCTs) — the "gold standard" of medical research — simply aren′t suited to the assessment of nutritional supplements (1).

The crucial difference between nutrients and drugs is that drugs are foreign to the body. Drugs interfere in metabolism and are useful only when this interference halts or slows a disease process. Nutrients, on the other hand, support metabolic functions; supplements are taken to ensure an adequate supply of essential nutrients. Put differently, drugs are used to treat disease whereas nutritional supplements are taken to prevent disease and optimize health. This makes all the difference when assessing drugs and supplements.

In randomized placebo-controlled trials a substance is compared to a placebo (treatment versus control group). Control groups are readily available for drug trials since the drug doesn′t occur in nature. In contrast, everyone has some — usually sub-optimal — level of essential nutrients, i.e. there can be no genuine control group. It is impossible to carry out true placebo-controlled nutrient studies.

Drugs interfere in physiological processes and usually act quickly. Drug trials can therefore be completed in a reasonably short time, Nutritional deficiencies, on the other hand, may take years or even decades to lead to symptoms. Clinical trials of that length of time would be prohibitively expensive.

Clinical trials of single drugs make sense since every drug has an effect of its own. Nutrients, on the other hand, work together; all essential nutrients have to be present in adequate amounts for optimal health. Clinical trials of individual nutrients are pointless.

Of course, there are numerous other differences between drugs and nutritional supplements. Most importantly, drugs have dangerous side effects and need to be monitored carefully. Nutrients, on the other hand, have wide safety margins.

All this is obvious, yet large sums of money are squandered on studying nutrients with tools developed for drug evaluation — with predictably inconclusive results. It is almost as if these trials are meant to fail.

It is actually quite hypocritical to demand that nutritional recommendations be backed by randomized controlled trials; most pharmaceutical therapies aren′t based on RCTs either! First, many drugs are prescribed for off-label use. Secondly, most people on prescription drugs take more than one medication. Neither off-label nor multi-drug prescription is supported by the supposed medical "gold standard". A cynic might say that the concept of randomized controlled trials is mainly used to dismiss non-pharmaceutical therapies as unscientific".

Of course, nutritional recommendations should be based on scientific evidence. Just remember that it is not the need for nutrients that is in question, but rather the amounts that we need for optimal health. We may not know yet what those optimal nutrient levels are but, given today′s diets, most people will surely benefit from nutritional supplements.

Sources

Shao A, Mackay D, A commentary on the nutrient-chronic disease relationship and the new paradigm of evidence-based nutrition, Nat Med J 2010;2(12):10-18.
http://www.naturalmedicinejournal.com/pdf/NMJ_DEC10_LR2.pdf

Do we really need nutritional supplements?

2011-05-24T21:17:08Z

Do we really need nutritional supplements? Why couldn′t we get all the nutrients we need from a "balanced diet"? We probably could — if we ate right. But how many people eat right?

Apparently not too many. For example, there is a big gap between what Americans eat and the dietary recommendations outlined in Healthy People 2010. And things aren′t much better in other industrialized countries.

Healthy People 2010 recommends at least two daily servings of fruit, three servings of vegetables a third of which should be dark green or orange, and six servings of grains three of which should be whole grains. How closely did Americans follow this advice? National Health and Nutrition Examination Survey (NHANES) results showed (1) that in 2003 - 2004:

only 40% of children and adults ate the recommended 2 servings of fruits per day
only 7% of children and 11% of adults ate the recommened number of dark green or orange vegetables
54% of those surveyed ate the recommended number of servings of grains, but only 3% had 3 or more servings of whole grains

As scientists at the U.S. National Cancer Institute put it, "These findings add another piece to the rather disturbing picture that is emerging of a nation′s diet in crisis" (2).

State-run dietary surveys gave similarly dismal results (3). The 2007 data from the Behavioral Risk Factor Surveillance System (adults) and the Youth Risk Factor Surveillance System (grades 9 - 12) showed that:

only 32.8% of adults and 32.2% of adolescents ate 2 or more fruits per day
only 27.4% of adults and 13.2% of adolescents ate 3 or more vegetables
only 14.0% of adults and 9.5% of adolescents ate both 2 or more fruits and 3 or more vegetables per day

Things hadn′t improved two years later. The 2009 surveys found that still only 32.5% of adults consumed 2 or more servings of fruits and only 26.3% of adults had 3 or more servings of vegetables per day (4).

Are the dietary recommendations set out in Healthy People 2010 too difficult to live up to? If anything, they may not go far enough; the food pyramid developed by scientists at the Harvard School of Public Health places even greater emphasis on eating fruits, vegetables, and whole grains (5).

The Harvard Food Pyramid was developed in response to the undue influence that the powerful food industry lobby exerts on government-issued dietary guidelines. The Harvard scheme doesn′t recommend serving sizes — it simply ranks different food groups according to their known health benefits. The pyramid consists of four layers which contain, from top (least healthy) to bottom (healthiest):

butter, red and processed meat, refined grains, potatoes, sugary drinks and sweets
dairy products
nuts, seeds and tofu, and fish, poultry and eggs
fruits and vegetables, whole grains, and healthy fats and oils

Of course, food pyramids aren′t just about micronutrients, but the failure to consume enough fruits, vegetables and whole grains is a clear indication that most of us don′t get enough vitamins and minerals from our diets. The authors of the Harvard Food Pyramid in fact acknowledge this and recommend a daily vitamin/mineral supplement for most people (5).

Sources

Healthy People 2010, Progress review — Nutrition and overweight presentation, 2008.
http://www.cdc.gov/nchs/ppt/hp2010/focus_areas/fa19_2_ppt/fa19_nutrition2_ppt.htm
Krebs-Smith SM, Guenther PM, Subar AF et al, Americans do not meet federal dietary recommendations, J Nutr 2010;140(10):1832-1838.
http://dx.doi.org/10.3945/jn.110.124826
CDC State indicator report on fruits and vegetables, 2009.
http://www.fruitsandveggiesmatter.gov/downloads/StateIndicatorReport2009.pdf
State-specific trends in fruit and vegetable consumption among adults - United States, 2000 - 2009. Morbidity and Mortality Weekly Report, Centers for Disease Control and Prevention. 2010;59(35):1125-1130.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5935a1.htm?s_cid=mm5935a1_w
Food pyramids: What should you really eat?
http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/pyramid-full-story/index.html

P.S. I first published this article on Mike Adams′ NaturalNews site under the title "Americans lack nutrients because of poor eating choices". You can find all my NaturalNews pieces at http://naturalnews.com/author93.html.

Weight loss and exercise

2011-03-14T21:26:00Z

Back to the battle of the bulge and the series of articles that got me going on that subject. The first part in the series focused on whether exercise would help you lose weight.

Here is how the author introduces the subject (1):

"It′s such a widely accepted idea it′s virtually dieting dogma, a belief pushed with almost religious zeal: You can′t lose weight without exercising more."

and

"We have been taught that exercise is a surefire path to weight loss. But controversy is growing over whether working out to lose weight can be an exercise in futility. At issue is whether the amount of exercise needed to make a meaningful impact is unrealistic and whether gluttony, and not sluggishness, is where we should be focusing our efforts."

So, does exercise help you lose weight? As the introduction implies, the answer seems to be no. This is also the conclusion of a 2009 Time Magazine article (2) that ruffled quite a few feathers. The author of that piece quotes an exercise expert as saying that "In general, for weight loss, exercise is pretty useless … The common belief that physical activity can counteract rising rates of obesity is based on a belief rather than on solid scientific evidence.".

Why doesn′t exercise lead to weight loss? The typical explanation is that people don′t work out long enough or intensely enough (1):

"The amount of exercise needed to cause significant weight loss is more than most free-living individuals are capable of undertaking, and that is particularly true for the obese".

"You need a lot of exercise, and a lot of time, to make a 200, 300, 400 calorie deficit whereas you can easily make a 1,000 calorie deficit by cutting down your intake "

Of course, not everyone agrees that exercising to lose weight is futile, even in the face of evidence to the contrary. Here is my favourite quote — it demonstrates so beautifully just how misguided expert advice can be (1):

"[It] makes no difference to the human body whether it sheds calories via eating less or exercising more. The end result is the same: weight is lost."

This statement is only partially right. It really doesn′t seem to matter whether we shed calories by eating less or exercising more; the result appears to be the same all right. Unfortunately, the outcome isn′t weight loss, but rather a failure to lose weight.

What is wrong with the idea that all you have to do is create an energy deficit and you′ll lose weight?

Suppose you are overweight or obese. If you′re not losing weight this has to mean that all your energy needs are met by the food you eat. You now start a regular exercise routine hoping to lose weight, i.e. to burn some of your stored fat. Question: Why should your exercise fuel come from your adipose tissue, when all your other metabolic needs are met by food?

For exercise to lead to weight loss it would have to do more than just create an energy deficit. Exercise would have to draw on the fat reserves stored in the body′s adipose tissue, without replenishing those stores afterwards.

Just because exercise doesn′t help you lose weight, this doesn′t mean it is useless. Physical activity has many health benefits, such as increased cardiovascular fitness and insulin sensitivity, lower blood pressure, and improved mental health and cognitive ability. It just doesn′t seem to help you lose weight.

Sources:

Sharon Kirkey. Exercise alone doesn′t cut it. Canwest News Service March 6, 2010.
http://www.timescolonist.com/health/battle+cultural+epidemic/2660423/Exercise+alone+doesn/2649284/story.html
John Cloud. Why exercise won′t make you thin. Time Magazine August 9, 2009.
http://www.time.com/time/printout/0,8816,1914857,00.html

Junk food addiction and obesity

2011-03-13T23:42:00Z

The February 2011 issue of Scientific American ran an 8-page article on obesity which starts with this stark assessment of the situation:

"Obesity is a national health crisis — that much we know. If current trends continue, it will soon surpass smoking in the U.S. as the biggest single factor in early death, reduced quality of life and added health care costs … " (1)

That′s hardly an exaggeration. Obesity is a risk factor for cardiovascular disease and type 2 diabetes, two of the leading causes of premature death. In addition, the same lifestyle that leads to obesity also increases cancer risk. According to health experts from the Americal Institute for Cancer Research and the World Cancer Research Fund, simple lifestyle changes could prevent a third of all common cancers (2).

How did we ever get into this mess? By replacing real food and drink with processed junk. Not only is this stuff — you can′t call it nutrition — unhealthy but it is literally addictive (3). Food and drug abuse affect brain function in similar ways, and junk food eating patterns resemble drug addiction — binge eating, an inability to stop even though one is aware of adverse health consequences, an increase over time in the frequency and quantity of junk food eaten, etc. Small wonder then that the author of the SciAm article considers behaviour modification techniques developed for dealing with addiction to be society′s best hope for combatting the obesity epidemic:

"Behavior-focused studies of obesity and diets as early as the 1960s recognized some basic conditions that seemed correlated with a greater chance of losing weight and keeping it off: rigorously measuring and recording calories, exercise and weight; making modest, gradual changes rather than severe ones; eating balanced diets that go easy on fats and sugar rather than dropping major food groups; setting clear, modest goals; focusing on lifelong habits rather than short-term diets; and especially attending groups where dieters could receive encouragement to stick with their efforts and praise for having done so." (1)

Is this where we are headed? One of life′s most basic and pleasurable activities — eating — needs to be guided and supervised by behavioural psychologists, with therapy group meetings for reinforcement? We can′t seem to prevent the food processing industry from hooking us on their addictive junk, so we′ve created another industry, the weight loss industry complete with psychologists and therapy groups, to help us manage our addiction to the stuff.

Admittedly, some pressure is now being applied to the food industry to stop their nefarious business practices, but we still have a long way to go. Take the case of McDonald′s "Happy Meals". Apparently, the company gives away some cheap junk toy with every so-called Happy Meal. The kids want the toy and nag their parents until they get what they want. Clearly, McDonald′s manipulates parents through their children into buying junk food, and good luck to any parent trying to resist. This is about as blatant an example of manipulating children as you will find, yet there is opposition to banning the practice; such regulations are considered by many to be too intrusive (1).

We are in the grips of an ideology called capitalism, the naive belief that everyone′s selfish actions will automatically optimize the common good. This "invisible hand" may have worked in Adam Smith′s day, but it doesn′t work in this age of multinational corporations.

Power tends to corrupt; we have no trouble seeing this in the political arena. So why is it so difficult to recognize that economic power corrupts just as much, even in the face of the outrageous criminal behaviour of big multinational corporations in recent years. In fact, vested business interests arguably do more to corrupt the political process than political ambition. And this happens in broad daylight — it′s called lobbying.

Where does this naive belief in the automatic benefits of capitalism get us? A publicly traded company is expected to maximize financial returns for their share holders, but the company is perfectly free to sicken and kill those same share holders and their families with the junk they sell them in order to generate those financial returns.

Have we lost our way, or what?

Sources

David H. Freedman. How to fix the obesity crisis. Scientific American, February 2011.
Kate Kelland. Simple life changes could stop millions of cancers. Reuters, February 4, 2011.
Gearhard AN, Corbin WR, Brownell KD, Preliminary validation of the Yale Food Addiction Scale. Appetite (2009), doi:10.1016/j.appet.2008.12.003
http://dx.doi.org/10.1016/j.appet.2008.12.003

A simple idea for a heart-healthy Valentine′s Day treat

2011-02-05T01:11:00Z

Looking for a different Valentine′s Day treat this year? Create your own chocolate berry/fruit and nut clusters! They are easy to make and the ingredients — chocolate, dried fruits or berries, and nuts like almonds, cashews, pecans or hazelnuts — are inexpensive and readily available in the bulk food section of any supermarket. Make sure though you buy quality dark chocolate, preferably the semi -sweet variety. Try the following recipe — it′s simple and delicious:

Chocolate almond cranberry clusters
200 g dark chocolate 75 g almonds 75 g dried cranberries
Cover a baking sheet with wax paper. Mix the nuts and berries. Heat the chocolate in a water bath and fold the berry/nut mixture into the melted chocolate, Grab a tea spoon, scoop out bite-size pieces of the mixture and drop them on the covered baking sheet; try to keep the clusters from touching. Refrigerate the whole thing for an hour or two and you have delicious chocolate almond cranberry clusters.

Appropriately enough for a Valentine′s treat, these chocolate clusters are actually quite heart-healthy — when consumed in moderation of course. All three ingredients contain polyphenolic and other antioxidants that have been shown to help reduce LDL oxidation, which in turn lowers the risk of atherosclerosis and cardiovascular disease. They contain many other important nutrients as well with additional health benefits. In fact, you′ll find nuts, berries, fruits, and even dark chocolate on every list of healthful snacks.

Use dried fruits like apricots, pineapples, papayas or prunes instead of cranberries. Try pecans, cashews, or hazelnuts instead of almonds. Use your imagination. Experiment!

Enjoy!

How close are we to genetic medicine?

2010-11-24T22:48:00Z

How close are we to genetic medicine?

A couple of posts ago ("The future of medicine, and other fantasies") I commented on a recent Scientific American article on the future of medicine (1). The author of the piece focused on the promises of stem cell research and potential payoffs from the genome project. I share his hopes for medical breakthroughs from stem cell research, but I find his take on genomic medicine rather naive:

“[The] one-size-fits-all medicine we have seen for the past 100 years will yield to medicine tailored to each individual. Doctors will prescribe a custom prevention program and make comprehensive diagnoses according to each patient′s genes, bacteria, allergens, fungi, viruses and immune system.

Studying the specific combinations of genes and environmental factors can lead to changes in diet, drugs and behavior, helping us extend our healthy years.

Your genome will get sequenced every year or so to check for the emergence of cancer cells, autoimmune cells, inflammation, and so on and will help predict what treatment may work best if a disease appears” (1)

What′s so improbable about this scenario? It ignores the causal role of the food and drug industries in our health crisis. How do you develop custom prevention programs, improve diet, and change behaviour while food companies do everything in their power to peddle junk food and drug companies maintain an iron grip on the medical profession and their "healing" monopoly?

The authors of two recent articles on the promise of genome-wide association studies (GWASs) — the prediction of disease risk from the patterns of genetic mutations — are a good deal more realistic in their assessment of the promise of genetic medicine (2,3). They point out that so far genome-wide screening has neither lived up to expectations nor is it clear that it would be cost-effective.

Genome-wide screening has identified a number of alleles (gene variants) associated with various diseases, but to date no major susceptibility alleles have been found; each of the known risk-associated alleles has at most a small effect on disease risk. Even their combination accounts for only a small percentage of known genetic risk variations, likely because the relationship between genetic variation and environment is as yet poorly understood:

"What is becoming clear from these early attempts at genetically based risk assessment is that currently known variants explain too little about the risk of disease occurrence to be of clinically useful predictive value." (2)

Even if GWASs led to reliable predictors of disease risk, population-wide screening would hardly be justified; medical expenses already threaten to bankrupt most industrialized countries. Screening everyone would at best identify those who are genetically predisposed to develop a certain disease but have no family history of that disease. Even then genetic screening would only be worthwhile if saving lives depended on identifying and treating individuals at risk before clinical symptoms appeared.

Genetic risk factors only predispose to disease; actual disease development depends on gene-environment interactions. Prevention would therefore mostly consist of lifestyle changes like smoking cessation, dietary improvements, and exercise. It is questionable whether the threat of a possible future illness will motivate people to make the necessary changes; and without implementing preventive measures genetic screening is pointless:

"Before genetic information is used in public health screening, it must be shown that:

such information predicts disease risk better than phenotypic information;

cost-effective interventions exist for those at increased genetic risk;

these interventions are more cost-effective than population-level interventions;

genetic risk information motivates desired behaviour change.

Currently there are no examples of genetic screening for disease risk that satisfy these criteria." (3)

Sequencing the human genome was a major scientific achievement, but we are unlikely to derive significant health benefits from it. Population-wide lifestyle changes offer by far the greatest potential pay-off, and for that you don′t need your genome sequenced. Healthy living is a good idea for everyone, regardless of genetic make-up.

Sources:

Church G. Medicine I can call my own. In What comes next: Experts predict the future. Scientific American September 2010.
http://www.scientificamerican.com/article.cfm?id=what-comes-next&page=5
Feero WG, Guttmacher AE. Genomewide association studies and assessment of the risk of disease. New Engl J Med 2010;363(2):166-176.
http://content.nejm.org/cgi/reprint/363/2/166.pdf
Hall WD, Mathews R, Morley KI. Being more realistic about the public health impact of genomic medicine. PLoS Medicine 2010;7(10):e1000347.
http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000347

The future of medicine, and other fantasies

2010-09-03T00:15:00Z

Scientific American asked ten 'visionary' science experts on its advisory board to tell the world what societal changes they foresaw for the coming decades. You can read the results of their cogitations in SciAm′s August 26, 2010 online edition (1). I myself was mainly interested in what they had to say on the subjects of health and medicine.

George Church's piece "Medicine I can call my own" focuses on the promises of stem cells and affordable genome sequencing. Stem cells hold promise for regenerative medicine. Mapping each patient′s genome should, in the author′s opinion, lead to customized diagnoses, treatments, and diets:

"In the near future, a complex ecosystem of health care and software providers will empower doctors to treat each patient as a unique individual. Your stem cells will be fashioned into ad hoc treatments. Your genome will get sequenced every year or so to check for the emergence of cancer cells, auto-immune cells, inflammation, and so on and will help predict what treatment may work best if a disease appears. Not just knowing but shaping your biology will be part of your life." (1)

The piece reminded me of Thomas Edison′s optimistic prediction:

"The doctor of the future will give no medicine, but will interest her or his patients in the care of the human frame, in a proper diet, and in the cause and prevention of disease." (2)

Edison′s prediction obviously didn′t come true. What happened instead was that Big Pharma took control of the American medical system. Here is how economist Paul Zane Pilzer put it in 2001:

"Sadly, most physicians have become 'technology dispensers' for the products and services of the large multinational medical companies — companies which always seem to tip the scale between profits and patients in favor of profits. In some cases this means manipulating the federal government against the public interest in safety as well as in dollars." (3)

Not only does the pharmacutical industry have no interest in your wellbeing — you are more profitable to them chronically ill than healthy — but neither does the food industry. In fact, both food and drug companies will try to suppress perfectly sound health claims through their influence on regulatory agencies, to protect their profits. Pilzer again:

"While there is obviously no direct conspiracy between the $1 trillion food industry (which causes most of the problems) and the $1.4 trillion medical industry (that treats just enough of the symptoms to get the 'targets' back to work and consumption) the economic effect is the same as if these two industries were conspiring against the American consumer in the most sinister fashion.

On a microeconomic level, each time consumers get real information that could help them take control of their health, the food and medical industries, acting in their own economic self-interest, manipulate this information against them." (3)

Pilzer wrote about the American situation and for an American audience, but these problems aren′t unique to the U.S. Just a couple of days after they gave us a glimpse of the future as they saw it, Scientific American offered us this gem: Researchers at Imperial College London actually proposed that restaurants serving things like cheeseburgers and milkshakes ought to include a statin pill with each order to "offset the health risks of the high fat meal" (4).

Would you take health advice from doctors like these? Yet, the medical establishment has been very successful in equating good health with good medical care in people′s minds. For example, both Thomas Edison and the writer of the SciAm piece took it for granted that health is the purview of medicine. Similarly, the terms 'health care' and 'medical care' are used interchangeably by far too many writers.

Good health is largely the result of a proper diet and exercise, etc. You don′t need your genome sequenced to know whether junk food is right for you or not, and you can find better sources of health information than your family doctor. Most physicians don′t know much more about nutrition than their patients; the subject isn′t even taught in most medical schools!

I do hope that stem cell research and the genome project will lead to medical breakthroughs; we need access to quality medical care even if we make every effort to adopt a healthy life style. But drugs cannot compensate for a lousy diet and a lack of exercise, and bad life style choices will undo any benefits that medical advances might bring.

But they can keep their 'complex ecosystem of health care and software providers' that is supposed to empower doctors to treat each patient as a unique individual. A 'complex ecosystem of lobbyists and drug reps' to control doctors and protect Big Pharma′s interests is far more likely anyway.

Sources

Church G. Medicine I can call my own, in What comes next: Experts predict the future. Scientific American online, August 26, 2010.
http://www.scientificamerican.com/article.cfm?id=what-comes- next&print=true
The Quotations Page.
http://www.quotationspage.com
Paul Zane Pilzer. The next trillion. Abridged Version. VideoPlus 2001.
Karen Hopkin. Researchers recommend statins with your fries. Scientific American August 26, 2010.
http://www.scientificamerican.com/podcast/episode.cfm?id=researchers- recommend-statins-with-10-08-26

Some thoughts on weight control

2010-03-15T21:36:00Z

Our local paper just ran a three-part series on the battle of the bulge. Nothing unusual about that; you can hardly open a paper or magazine without coming across something on weight loss. I must say though that I find much of what has been written on this subject simple-minded or outright nonsensical. What good is advice like 'all you have to do is eat fewer calories than you expend'. If it were so simple, why would so many people be fat?

Do I have all the answers? Of course not — nobody does; there is no concensus among experts on what caused this obesity epidemic and how to solve the problem. There are, however, a few observations that would seem obvious, yet are ignored in much of what is written on the subject.

We have hormones that control how much we eat

All animals, including humans, have elaborate hormonal control systems in place to ensure an adequate energy supply — it′s a matter of survival and can′t be left to willpower. Imagine a lioness wondering 'should I eat the rest of this zebra, or is my ass getting too big'.

This hormonal control system works very accurately

Have you ever seen obese wildlife? The only animals that end up obese are those whose food we control — life stock, pets, lab animals.

One third of the population still keeps their weight in a narrow range throughout their adult lives; fifty years ago that was true of the majority.

This hormonal control system works well in obese people too — it just doesn′t work quite well enough

To show that this is so we need some numbers. Suppose you gained just 5 lb every year. In 10 years you would be 50 lb heavier, in 20 years you′d carry around an extra 100 lb, etc. In other words, gaining just 5 lb per year will make you grossly obese. Most of the overweight and obese gain weight more slowly than that.

How many extra calories would you take in if you gained 5 lb? Since 1 lb of fat gives you about 3,500 Kcal, you would take in an extra 5 × 3,500 = 17,500 Kcal/year. Dividing this by 365 gives you roughly 48 additional Kcal/day. At a daily intake of ≈ 2,000 Kcal, an additional 48 Kcal would exceed your daily energy expenditures by just 48 ÷ 2,000 ≈ 2.5%.

In other words, if your hormonal control is out by just 2 or 3 percent you′ll end up grossly obese. Put differently, even the grossly obese still balance energy intakes and expenditures to within 2 or 3 percent; pretty accurate I′d say.

If you are too heavy and aren′t losing weight then all your fuel must come from food

If you are overweight or obese you have two potential fuel sources — your fat reserves and food. If your weight is stable this means that all the fuel you burn comes from the food you eat; a net use of stored fat would result in weight loss.

If you are still gaining weight then there is obviously no net withdrawal of stored fat; your food provides all your energy needs, and then some.

You cannot improve on this hormonal control system — even if it would let you

Say you want to count the calories you eat. You′d have to weigh and measure the amount of food you eat, and you′d need to know its energy content.

First, kitchen scales aren′t accurate enough to weigh food to within a percent or two. Secondly, different foods have different energy contents; 100 g green beans ≠ 100 g dry beans ≠ 100 g chicken breast. You′d have to consult food composition tables, which only give you averages anyway. How many people would do that? Thirdly, we don′t just eat staple foods of known energy content — we cook with them. Do you really think you can determine the energy contents of 100g of your homemade stew to a couple of percent?

Forget portion control and calorie counting! The idea that your head can do better than your hormones at balancing energy input and output is laughable.

You cannot override this hormonal control system — it won′t let you

So you′ve decided to eat fewer calories than your body needs, in the hope of activating your fat reserves. That′s called dieting.

If deliberately cutting back on your calorie intake, aka dieting, worked there would be no weight loss industry, no obesity research, no medical specialty called bariatrics, and no endless stream of advice on 'how to lose weight and keep it off'; the very term 'dieting' would have no meaning.

So where does all this leave us?

As I see it, this leaves us with two obvious questions:

why is there a slight imbalance between energy intake and expenditure in the overweight and obese, and
why do the overweight and obese not mobilize their fat reserves

We need to understand why energy intake and expenditure aren′t always completely balanced to stop obesity. And we need to understand why the body doesn′t use its fat reserves to reverse it.

Micronutrient deficiencies, DNA damage and degenerative diseases

2010-03-04T20:54:00Z

In my last post I talked about micronutrient triage. When micronutrients — vitamins and minerals — are in short supply they are preferentially allocated to physiological functions crucial for survival; maintenance and repair are temporarily put on hold (1). If our diets are chronically deficient in micronutrients, the prolonged neglect of vital repair functions is bound to take its toll.

That vitamins and minerals play a crucial role in health and disease should come as no surprise. Vitamins are defined as substances that the body needs but cannot make; and we obviously cannot make minerals. Vitamins and minerals act as antioxidants, stabilize protein structures and are enzyme cofactors. They are involved in all aspects of physiology, starting with such fundamental processes as DNA maintenance and gene expression.

Inefficient or incorrect DNA repair due to micronutrient shortages leads to genome instability, a known contributor to increased cancer risk, accelerated aging and neurodegenerative diseases (2). Genome damage caused by micronutrient deficiencies is believed to be at least as extensive as genome damage from environmental genotoxins like chemical carcinogens, UV and ionizing radiation. Genome instability caused by micronutrient deficiencies in turn increases DNA sensitivity to environmental genotoxic stressors.

Since degenerative diseases, the main health problems in the developed world, are partly caused by DNA damage, it makes sense to diagnose and nutritionally prevent the underlying cause, genome instability. This requires a knowledge of optimal intakes for vitamins and minerals that are needed to prevent DNA damage (2):

"Excessive genome instability, a fundamental cause of disease, is often an indication of micronutrient deficiency and is therefore preventable
accurate diagnosis of genome instability using DNA damage biomarkers that are sensitive to micronutrient deficiency is technically feasible
it should be possible to optimise nutritional status and verify efficacy by diagnosis of a reduction in genome damage rate after intervention"

Vitamins C, E, B₂, B₆, B₁₂, folate and niacin, and the minerals zinc, iron, magnesium and manganese are some of the micronutrients known to be critical to genome stability (2). Optimal intakes of most of these micronutrients have not yet been determined, but for those that have been studied — e.g. folate and vitamin B₁₂ — intakes in excess of current RDA values are required to prevent genome damage. Optimal micronutrient intakes will also vary with people′s genetic make-up.

Optimizing micronutrient intakes seems like a promising way to reduce the degenerative disease burdens threatening to bankrupt medical care systems:

"… instead of diagnosing and treating diseases caused by genome damage, health and medical practitioners will be trained to diagnose and nutritionally prevent the initiating cause, i.e. genome instability itself." (2).

We′ll see.

Sources:

Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce resources by triage. Proc Natl Acad Sci USA 2006;103(47):17589-17594.
http://www.pnas.org/content/103/47/17589.full.pdf
Fenech M. Nutritional treatment of genome instability: a paradigm shift in disease prevention and in the setting of recommended dietary allowances. Nutr Res Rev 2003;16:109-122.
http://dx.doi.org/10.1016/S0278-6915(02)00028-5

Chronic micronutrient deficiencies lead to degenerative diseases

2010-02-23T23:12:00Z

When our bodies are starved of oxygen, blood flow is redirected from non-vital organs to those crucial for survival - the heart, brain and adrenal glands (1). This is an example of physiological triage — a survival mechanism.

Could micronutrients also be allocated by triage in times of shortages? According to Prof. Bruce Ames the answer is yes (1). When micronutrients — vitamins and minerals, as well as other biochemicals like omega-3 polyunsaturated fatty acids — are in short supply, available micronutrients are first used for life-preserving physiological functions.

Problem solved? In the short run, yes. But in the long run we pay a heavy price for chronic deficiencies in micronutrients; the forced neglect of vital maintenance functions like DNA repair, immune function and other systems not needed for immediate survival eventually leads to health problems. Micronutrient shortages have been linked to mitochondrial damage resulting in increased free radical production, cell damage and late onset diseases like cancer (1).

Because vital bodily functions remain unimpaired in times of micronutrient deficiencies, the problem may unfortunately not be noticed for some time; neglect of DNA repair doesn′t manifest itself immediately in clinical symptoms. We can go on for quite some time falsely believing that we are getting all the nutrients we need from our "balanced diet". Once clinical symptoms appear the damage is done.

Is micronutrient deficiency really such a problem? Unfortunately, the answer is yes. For example, the 2001-2002 National Health and Nutrition Examination Survey (NHANES) found that micronutrient shortages are widespread in the U.S. population (1). Many of the participants in that study had vitamin and mineral intakes below the Estimated Average Requirement (EAR). EAR values are even lower than recommended Dietary Allowance (RDA) values, which in turn are widely believed to be inadequate (2). The situation in other industrialized countries isn′t any better.

Micronutrient deficiency is definitely a problem. Since our eating habits don′t change over time, any nutritional deficiencies are likely chronic. Supplementation is therefore a must for most of us. Taking a daily multivitamin-mineral (MVM) complex is an inexpensive and effective solution with big payoffs down the road:

“Micronutrient inadequacies are widespread in the population, and a MVM supplement is inexpensive. A solution is to encourage MVM supplementation, particularly in those groups with widespread deficiencies such as the poor, teenagers, the obese, African Americans, and the elderly, in addition to urging people to eat a more balanced diet.” (1)

Sources

Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce resources by triage. Proc Natl Acad Sci USA 2006;103(47):17589-17594.
http://www.pnas.org/content/103/47/17589.full.pdf
Doctors say, raise the RDAs now. Orthomolecular Medicine News Service, October 30, 2007.
http://orthomolecular.org/resources/omns/v03n10.shtml

What do doctors think of dietary supplements?

2009-10-24T02:20:00Z

"UK professor says supplements are a waste of time". That was one of the headlines in a recent edition of NutraIngredients.com (1). The article quotes a Scottish professor of nutrition and dietetics saying that "People who take multivitamin supplements are probably just wasting their money and boosting the profits of vitamin companies".

He isn′t the first to speak out against the use of dietary supplements. Earlier this year NutraIngredients.com commented on a study of supplement use among American children and adolescents participating in the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES) (2). About one third of children and youths between 2 and 17 in that survey took dietary supplements. The investigators suggested that "health care providers in the country should discourage the use of supplements by children with healthy diets" (2).

Last year NutraIngredients.com quoted a member of the Harvard School of Public Health saying that dietary supplements will not provide the nutritional boost a poor diet requires (3). His exact quote, "A supplement is called a supplement because it′s supposed to be supplementing a healthy lifestyle", is actually quite amusing and presumably not what he meant. He is saying in effect that you need supplements even if you follow a healthy lifestyle, which surely includes the proverbial "balanced diet". Proponents of dietary supplementation couldn′t have put it any better!

How widespread is this anti-supplement attitude among doctors? The Council for Responsible Nutrition (CRN), a trade association representing the dietary supplement industry, conducted a couple of surveys among health care professionals to find out. What they discovered was that dietary supplement use was just as common among health care professionals as among the general public.

The first CRN survey, conducted in 2007, questioned 900 physicians and 277 nurses about their thoughts on dietary supplements (4). The survey revealed that 51% of the doctors and 59% of the nurses took dietary supplements regularly, comparable to supplement use in the general population. 79% of the physicians and 82% of the nurses also recommended dietary supplements to their patients, whether they themselved took supplements or not. The list of supplements taken and recommended included things like fish oils, in addition to vitamins and minerals.

The second CRN survey, released in 2008, questioned around 1200 orthopedic specialists, cardiologists and dermatologists (5). Among the orthopedic specialists 73% took supplements themselves; 94% of those who took supplements also recommended them to their patients. For the cardiologists surveyed those figures were 57% and 86%, and for the dermatologists 75% and 79%. Even many of the doctors who did not take dietary supplements still recommended them to their patients.

Are these health care professionals "just as naive and gullible as the general public"? I doubt it. The doctors and nurses surveyed may not be nutrition experts, but they see the extent and consequences of poor eating habits and sedentary lifestyles in their medical practices; they just have to look at their patients′ expanding waistlines. How do you get obese on a "balanced diet"? Given the shear number of the overweight and the obese, how could most people possibly get all the micronutrients they need from the food they eat?

In 2007 investigators from the U.S. Centers for Disease Control and Prevention (CDC) examined the dietary habits of about 100,000 high school students to find out how many ate the recommended two servings of fruits and three servings of vegetables per day. The results of the survey, released just recently (6,7), were sobering. Only 32% got two daily servings of fruit and only 13% the recommended three servings of vegetable. Less than one in ten high school students surveyed ate enough of both. The adults questioned in the same survey didn′t do much better. So much for the balanced diet.

I let the Independent Vitamin Safety Review Panel, a group of physicians, academics and researchers, have the last word on this subject:

"In the past, over-conservative government-sponsored standards have encouraged dietary complacency. People have been led to believe that they can get all the nutrients they need from a 'balanced diet' of processed foods. That is not true. For adequate vitamin and mineral intake, a diet of unprocessed, whole foods, along with the intelligent use of nutritional supplements, is more than just a good idea: it is essential." (8)

Sources:

Shane Starling. UK professor says supplements are a waste of time. NutraIngredients.com Sept. 10, 2009.
http://www.nutraingredients.com/content/view/print/259495
Lorraine Heller. Most children don′t need supplements, says study. NutraIngredients.com Feb. 4, 2009.
http://www.nutraingredients-usa.com/content/view/print/235056
Shane Starling. Harvard professor slams supplements. NutraIngredients.com Jul. 7, 2008.
http://www.nutraingredients-usa.com/content/view/print/173318
Dickinson A, Boyon N, Shao A. Physicians and nurses use and recommend dietary supplements: report of a survey. Nutr J 2009;8:29
http://www.nutritionj.com/content/8/1/29
Lorraine Heller. Doctors reveal supplement recommendations. NutraIngredients.com Dec. 11, 2008.
http://www.nutraingredients-usa.com/content/view/print/229798
9 in 10 teens fall short on fruits and veggies. Associated Press Sep. 29, 2009.
http://www.msnbc.msn.com/id/33071814/ns/health-diet_and_nutrition/
State indicator report on fruits and vegetables. Department of Health and Human Services, Centers for Disease Control and Prevention.
http://www.fruitsandveggiesmatter.gov/downloads/StateIndicatorReport2009.pdf
Doctors say, raise the RDAs now. Orthomolecular Medicine News Service Oct. 30, 2007.
http://orthomolecular.org/resources/omns/v03n10.shtml

Pharma tricks - ghostwriters part 2

2009-09-18T23:37:00Z

"If you are an editor, author, reviewer, or reader of medical journals, or if you depend on your doctor or health care provider getting unbiased information from medical journals, then the 1,500 documents now hosted on the PLoS Medicine Web site [1] should make you very concerned and angry. Because, quite simply, the story told in these documents amounts to one of the most compelling expositions ever seen of the systematic manipulation and abuse of scholarly publishing by the pharmaceutical industry and its commercial partners in their attempt to influence the health care decisions of physicians and the general public."

So starts an editorial, "Ghostwriting: The dirty little secret of medical publishing that just got bigger", in the September 2009 issue of PLoS Medicine (1). This is not the first time that PLoS editors and contributors have spoken out against this practice. What is different this time around is that a clear paper trail detailing these shenanigans surfaced in the course of litigation involving Wyeth and its HRT drug Prempro. Lawyers for PLoS Medicine and the New York Times were instrumental in getting these documents made public (2), and the New York Times ran a piece about this in their Aug 4, 2009 edition (3).

What is medical ghostwriting? The term refers to the Pharma practice of having writing firms produce manuscripts to the company′s specifications, paying "respected" academics to pose as authors, and getting these articles published in medical journals — without acknowledging the company′s involvement of course. As the PLoS Medicine editors put it:

"…articles highlighting specific marketing messages written by unattributed writers, but "authored" by academics, are strategically placed in the medical literature …" (2).

These ghostwritten articles are typically reviews favourable to drugs sold by the company commissioning the manuscript; benefits are exaggerated and side effects are minimized. However, even research papers and clinical trial results may be "authored" by ghostwriters. As cruder methods of persuasion lost their effectiveness, pharmaceutical companies turned to "educating" and influencing medical doctors by faking scholarly articles and submitting them to respectable academic publications.

"What, a cynical reader might ask, can I truly trust as being unbiased? The answer is that, sadly, for some or even many journal articles, we just don't know." (1)

The term "ghostwriting" is actually a bit misleading. It isn′t the writing firms that are the problem; it′s the academics posing as authors. Their names and reputations give credence to articles that are little more than ads masquerading as scholarly publications; the unsuspecting reader can′t tell the difference. Clearly, these "authors"and the pharmaceutical companies recruiting them are guilty of fraud.

"How did an industry whose products have contributed to astounding advances in global health over the past several decades come to accept such practices as the norm?" (1)

Well, judging by the recent scandals in the banking and financial sectors, corruption seems to be endemic in American business. Power tends to corrupt, Lord Acton said. Big Business is certainly powerful, and they are proving him right.

Sources:

The PLoS Medicine Editors. Ghostwriting: The dirty little secret of medical publishing that just got bigger. PLoS Medicine 2009;6(9):e1000156.
http://dx.doi.org/10.1371/journal.pmed.1000156
Wyeth ghostwriting archive. PLoS Medicine.
http://www.plosmedicine.org/static/ghostwriting.action
Natasha Singer. Medical papers by ghostwriters pushed therapy. NY Times Aug 4, 2009.
http://www.nytimes.com/2009/08/05/health/research/05ghost.html

Could you be suffering from orthorexia nervosa?

2009-09-14T22:45:00Z

You say you never heard of orthorexia nervosa? Well, neither had I until I read Jenny Thompson′s article "April [Fool′s Day] in August" in the September 8, 2009 edition of the HSI e-Alert (1). Here is how she introduced the subject:

"Do you read nutrition labels to avoid hidden trans fats, harmful additives, and sugar-substitutes? Do you choose organic foods to keep your intake of pesticides and herbides to a minimum? Do you even go out of your way to purchase free-range meat so you′ll get a maximum of omega-3 fatty acids and a minimum of trace antibiotics and growth hormones? If you answered yes to any of these questions, don′t be surprised if your doctor breaks the bad news: You have an eating disorder."

That supposed eating disorder — orthorexia nervosa — is an obsession with healthy eating, an obsessive compulsive disorder centered around food.

Here is what an article in the Observer (2) had to say about this grave new "disease":

"Eating disorder charities are reporting a rise in the number of people suffering from a serious psychological condition characterised by an obsession with healthy eating. The condition, orthorexia nervosa, affects equal numbers of men and women, but sufferers tend to be aged over 30, middle-class and well-educated."

A serious psychological condition characterized by an obsession with healthy eating? Hm.

"I am definitely seeing significantly more orthorexics than just a few years ago", the chairwoman of the mental health group of the British Dietetic Association was quoted as saying. "[Orthorexics] are solely concerned with the quality of food they put in their bodies, refining and restricting their diets according to their personal understanding of which foods are truly ′pure′."

What kinds of foods do these seriously disturbed orthorexics refuse to touch? Sugar, salt, caffeine, alcohol, wheat, gluten, yeast, soya, corn, and dairy foods are mentioned, as well as anything likely to contain pesticides, herbicides, and artificial additives. A bit strict maybe, but hardly a sign of a serious psychological problem. Even mainstream nutritionists warn against excess sugar, salt, and alcohol consumption. Gluten (wheat) as well as dairy products cause problems for many, and when did unfermented soy beans become food? I also try to avoid pesticides and herbicides; I should think you do too.

Who came up with this new-fangled disease called "orthorexia nervosa"? The term was introduced in 1997 by one Steven Bratman, M.D., who describes the affliction this way:

"Many of the most unbalanced people I have ever met are those who have devoted themselves to healthy eating. In fact, I believe some of them have actually contracted a novel eating disorder for which I have coined the name ′orthorexia nervosa.′ The term uses ′ortho,′ meaning straight, correct, and true, to modify ′anorexia nervosa.′ Orthorexia nervosa refers to a pathological fixation on eating proper food." (3)

"[people concerned with healthy eating] are sometimes affectionately called ′healthfood junkies.′ However, in some cases, orthorexia goes beyond a mere lifestyle choice. Obsession with healthy food can progress to the point where it crowds out other activities and interests, impairs relationships, and even becomes physically dangerous. When this happens, orthorexia takes on the dimensions of a true eating disorder, like anorexia nervosa or bulimia." (4)

To better understand Bratman and his "disease", one has to read his (short) original essay on orthorexia (3). It describes his experience with the lunatic fringe of the health food movement at a commune of health fanatics. He himself was part of that commune, before he was brought back to his senses; he is a "recovering orthorexic" himself. On reading this article (3) it becomes clear that he doesn′t apply the term orthorexia nervosa to people who simply focus on healthy eating. It is meant to describe someone with cockamamie ideas about food and a tendency toward obsessive compulsive behaviour.

Bratman is apparently quite sincere in his belief that orthorexia nervosa is an affliction to be taken seriously, a genuine disease requiring treatment. I suppose such misguided eating can actually lead to health problems. But does your typical "orthorexic" believe he needs treatment? And would he take nutritional advice from the medical establishment? Mainstream nutritional advice may be less extreme, but can be just as wrong-headed (dangers of cholesterol and saturated fat, etc).

I have to admit though that the term orthorexia nervosa appeals to my sense of humour. The lunatic fringe of the health food movement deserves a good ribbing, and orthorexia nervosa describes them wonderfully well. Still, there is something very sad about the extent to which we have lost our way in such a simple everyday matter as food.

Sources:

Jenny Thompson. April in August. HSI eAlert Sep 8, 2009.
http://mail.live.com/default.aspx?wa=wsignin1.0
Amelia Hill. Healthy food obsession sparks rise in new eating disorder. The Observer Aug 16, 2009.
http://www.guardian.co.uk/society/2009/aug/16/orthorexia-mental-health-eating-disorder
Steven Bratman, M.D.. Original essay on orthorexia.
http://orthorexia.com/index.php?page=essay
Steven Bratman, M.D.. What is orthorexia?
http://orthorexia.com/Index.php?page=katef

Lifestyle factors and chronic disease

2009-09-06T21:31:00Z

If we were asked to name the leading causes of death, most of us would name cardivascular disease and cancer. These are indeed the primary pathophysiological conditions identified at the time of death, but they are not the root causes. Diseases are the result of a combination of (unmodifiable) genetic and (modifiable) lifestyle factors. The real question therefore is what factors make the most significant contributions to these and other diseases.

A 1993 paper (1) attempted to answer that question. The authors searched the scientific literature from 1977 to 1993 for articles that quantitatively related lifestyle factors with disease. Coupled with actual U.S. death rates for 1990, they arrived at the following table of top risk factors and associated death tolls:

tobacco 400,000
diet/activity patterns 300,000
alcohol 100,000
microbial agents 90,000
toxic agents 60,000
firearms 35,000
sexual behavior 30,000
motor vehicules 25,000
illicit drug use 20,000

These ten factors (poor diet and sedentary lifestyle were lumped together) were estimated to account for about 50% of all U.S. deaths in 1990. Smoking, bad diets and lack of exercise are seen to be by far the major problems, accounting for 19% and 14% of all deaths, respectively.

The authors of a 2004 paper (2) put the U.S. death toll from smoking and poor diet/physical inactivity, the leading causes of death in the 1993 article, at 430,000 and 400,000, respectively. Their estimates are based on a survey of the relevant literature from 1980 to 2002 and actual numbers of U.S. deaths in 2000. As these authors point out, poor diet and lack of physical activity may soon overtake smoking as the leading cause of death in the United States.

The authors of a 2009 paper (3) analyzed data from the Potsdam, Germany, segment of the multi-center European Prospective Investigation Into Cancer (EPIC-Potsdam) study to estimate the risks associated with smoking, poor diet, lack of physical activity and high body mass index (a rather strange choice, given its dependence on diet and activity level). People who had none of these risk factors turned out to be 78% less likely to develop any chronic disease compared to those who smoked, ate poorly, were inactive and too heavy. Specific risk reductions were estimated to be 93% for diabetes, 81% for heart attacks, 50% for stroke, and 36% for cancer.

The authors of these papers emphasize that their numbers are only rough estimates of the death toll from perfectly avoidable risks. But these figures show very convincingly just how many of our chronic health problems are self-inflicted.

Sources

McGinnis JM, Foege WH. Actual causes of death in the United States. JAMA 1993;270(18):2207-2212.
http://jama.ama-assn.org/cgi/reprint/270/18/2207
Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA 2004;291:1238-1245.
http://jama.ama-assn.org/cgi/content/abstract/291/10/1238 [Free Abstract]
Ford ES, Bergmann MM, Kröger J, Schienkiewitz A, Weikert C, Boeing H. Healthy living is the best revenge. Findings from the European Prospective Investigation Into Cancer and Nutrition - Potsdam Study. Arch Intern Med 2009;169:1355-1362.
http://archinte.ama-assn.org/cgi/reprint/169/15/1355

Where will future antibiotics come from?

2009-09-03T04:19:00Z

In the Aug 27, 2009 edition of The Scientist a UCLA infectious disease specialist makes an impassioned plea to help push for funding for the development of new antibiotics (1). Brad Spellberg, the author of a new book on the antibiotic resistance crisis, Rising plague (2), entreats scientific and lay communities for help in the quest for new weapons against antibiotic-resistant bacteria:

"This crisis will not be averted without your support, without a grassroots movement to put pressure on all sides — political, medical, pharmaceutical, and consumer — to band together to act. I will tell you what can be done, but we need your help to do it." (1)

Why does he need our help? Don′t we have the pharmaceutical industry to save us and keep us healthy? Apparently not:

"The problem here is not scientific. New antibiotics are dying before they have a chance to enter the marketplace due to a murky regulatory landscape and also due to unfavorable economics (i.e., the relatively low rate of return on investment afforded by sales of short-course antibiotics compared to sales of drugs for chronic conditions, such as hypertension, dementia, cancer, arthritis, and high cholesterol). Big Pharma has largely exited the scene. (1) [emphasis added]

Does he really mean to say that the wealthiest of all the multinational companies are unwilling to fund the necessary work, just because there is more money to be made elsewhere — even if our very survival is at stake? And I thought "capitalism" and "free markets" would solve all our problems!

Sources:

Spellberg B. Rising Plague. The Scientist Aug 27, 2009.
http://www.the-scientist.com/news/display/55951/
Brad Spellberg. Rising plague: The global threat from deadly bacteria and our dwindling arsenal to fight them. Prometheus Books, Amherst, New York, 2009.

Fish oils reduce risk of cardiovascular disease

2009-08-20T04:33:00Z

In my last two posts I talked about the importance of ω3 polyunsaturated fatty acids (PUFAs). In this post I want to focus on their role as precursors for a group of hormone-like substances collectively known as eicosanoids. The information presented here is largely taken from a recent review article on dietary lipids in inflammatory disorders like cardiovascular disease (1). Some of that material is also summarized on a couple of U.S. National Institutes of Health (NIH) websites (1).

Our bodies make these eicosanoids from two C-20 polyunsaturated fatty acids, the ω3 PUFA eicosapentaenoic acid (EPA) and the ω6 PUFA arachidonic acid (AA). Eicosanoids regulate important physiological functions like inflammation (prostaglandins), blood clotting (thromboxanes), and the immune response (leukotrienes). These are obviously vital defense mechanisms, but when they get out of hand the result is tissue damage and disease.

What could cause these defense mechanisms go awry? Physiological responses regulated by the ω6 PUFA derivatives are usually much stronger and more dangerous than the hormonal effects of EPA-derived prostaglandins, thromboxanes or leukotrienes. Imbalances in the ω3/ω6 ratios therefore have serious health consequences. The higher the ω6/ω3 eicosanoid ratio, the greater the danger of overreaction and disorders like chronic inflammation.

What determines the eicosanoid ω3/ω6 ratio? We can make neither ω3 nor ω6 PUFAs; they have to come from our diets. The ω3/ω6 eicosanoid ratio in our fat stores simply reflects the dietary mix of ω3 and ω6 polyunsaturated fatty acids, This in turn determines the ω3/ω6 ratio of PUFAs incorporated into cell membrane phospholipids, the precursors for eicosanoid synthesis.

Our bodies don′t seem to preferentially make either ω3 or ω6 eicosanoids. Phospholipid-bound ω3 and ω6 PUFAs are equally likely to be released and used as precursors. The elongation of shorter PUFAs to the C-20 fatty acids — linoleic acid to AA and α-linolenic acid to EPA — is catalized by the same enzymes. Other enzymes convert both EPA and AA to eicosanoids, and the ω3- and ω6-derived eicosanoids compete for the same receptors.

There are some quantitative differences in conversion rates and receptor binding between ω3 and ω6 eicosanoids. Nevertheless, the ω3/ω6 eicosanoid ratios are largely determined by the mix of phospholipid-bound ω3 and ω6 PUFAs, and therefore ultimately by the dietary ω3/ω6 mix. There is a clear correlation between the phospholipid PUFA fraction belonging to the ω6 series and death from cardiovascular disease — the higher the ω6 percentage, the greater the death toll (1).

What causes this ω3/ω6 PUFA imbalance in our diets? It is largely due to the excessive consumption of vegetable oils. Canola oil has the least unfavourable ω3/ω6 ratio at about 1:2. That ratio for corn oil is about 1:9, and the other commonly used oils aren′t any better. You can find a table of PUFA compositions for the more common cooking oils on one of the NIH websites quoted in the reference list (1).

Rebalancing the ω3/ω6 polyunsaturated fatty acid mix really requires both a reduction in dietary ω6 PUFA intake and an increase in ω3 PUFA consumption. Given the accumulated excess of ω6 PUFAs in our tissues, taking fish oils is much more effective than adding α-linolenic acid from sources like flax seeds. The conversion from the C-18 PUFA α-linolenic acid to EPA is simply too inefficient; preformed EPA itself is 15 times more effective at raising EPA levels than α-linolenic acid (2).

Compensating for excess ω6 fatty acids is by no means the only role of ω3 fatty acids, nor are imbalances in eicosanoids solely responsible for cardiovascular disease. There can be little doubt, however, that imbalances in dietary polyunsaturated fatty acid intake contribute to heart disease. This connection is both firmly established clinically and physiologically plausible.

So, Eat fatty fish or take EPA/DHA supplements! It is a simple and effective way to reduce your risk of cardiovascular disease and other inflammatory disorders.

Sources:

Lands B. A critique of paradoxes in current advice on dietary lipids. Progr Lipid Res 2008;47:77-106. See also
http://dx.doi.org/10.1016/j.plipres.2007.12.001 [Free Abstract]
http://ods.od.nih.gov/eicosanoids/ and
http://efaeducation.nih.gov/
Brenna JT, Salem Jr. N, Sinclair AJ, Cunnane SC. α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukotrienes Essential Fatty Acids 2009;80:85-91.
http://www.plefa.com/article/S0952-3278(09)00016-7/abstract [Free Abstract]

Cardiovascular disease and omega-3 fatty acids

2009-07-27T21:37:00Z

In my last post I reviewed an article about health risk factors and premature deaths (1). One of the authors′ more surprising findings was that, in the U.S. alone, an estimated 84,000 lives could be saved annually if everyone′s omega-3 fatty acid intakes were optimized, either through diet or supplementation. By comparison, cholesterol-lowering strategies were estimated to save about 113,000 lives annually. I was of course aware of the importance of n-3 (omega-3) fatty acids, but I was surprised by the numbers. Maybe I shouldn′t have been.

In 2003 the Nutrition Committee of the American Heart Association (AHA) had this to say about omega-3 fatty acids and cardiovascular disease (2):

"Omega-3 fatty acids have been shown in epidemiological and clinical trials to reduce the incidence of cardiovascular disease. Large-scale epidemiological studies suggest that individuals at risk for coronary heart disease benefit from the consumption of plant- and marine-derived omega-3 fatty acids, although the ideal intakes presently are unclear. Evidence from prospective secondary prevention studies suggests that EPA + DHA supplementation ranging from 0.5 to 1.8 g/day (either as fatty fish or supplements) significantly reduces subsequent cardiac and all-cause mortality. For α-linolenic acid, total intakes of ∼ 1.5 to 3 g/day seem to be beneficial."

The authors go on to say that even patients with existing heart disease can benefit from omega-3 supplementation (2):

"A dietary (i.e. food-based) approach to increasing omega-3 fatty acid intake is preferable. Still, for patients with coronary artery disease, the dose of omega-3 (∼1 g/day) may be greater than what can readily be achieved through diet alone. These individuals, in consultation with their physician, could consider supplements for CHD risk reduction. Supplements could also be a component of the medical management of hypertriglyceridemia, a setting in which even larger doses (2 to 4 g/day) are required."

In 2005 a meta-analysis of randomized controlled trials of the effects of various lipid-lowering interventions on all-cause and cardiovascular deaths appeared (3). In all, 97 trials involving nearly 140,000 patients and a roughly equal number of controls were included in that analysis. The lipid-lowering interventions consisted of statins, fibrates, resin, niacin, n-3 fatty acids or dietary intervention. This is how the authors summarized their findings (3):

"Statins and n-3 fatty acids are the most favorable lipid-lowering interventions with reduced risks of overall and cardiac mortality."

The actual risk ratios for all-cause mortality were 0.87 for statins and 0.77 for n-3 fatty acids. For death from cardiovascular disease the corresponding values were 0.78 for statins and 0.68 for n-3 fatty acids. The authors point out, though, that in the n-3 fatty acid intervention group the risk reduction was significant only in secondary prevention, i.e. for patients who already had cardiovascular disease.

They might have added that the reduction in the risk of death was even greater in the n-3 fatty acid than in the statin group, that n-3 fatty acids don′t come with the side effects of statins, and that they are a good deal cheaper as well.

The authors do suggest though that "future trials should explore whether n-3 fatty acids in combination with statins lead to additional reductions in coronary heart disease mortality, especially in patients with metabolic syndrome". It′s possible that combination therapy might confer additional benefits, since statins and n-3 fatty acids act differently. Statins reduce cholesterol synthesis, whereas n-3 fatty acids tame inflammation.

n-3 and n-6 polyunsaturated fatty acids are precursors for a group of hormone-like substances — summarily referred to as eicosanoids — which control, among other things, the body′s inflammatory response. Eicosanoids derived from n-6 fatty acids up-regulate inflammation, whereas n-3 eicosanoids keep it in check.

We cannot interconvert n-3 and n-6 fatty acids, which means that the dietary mix of n-3 and n-6 fatty acids determines our ability to initiate and control inflammation. Unfortunately, we get far too much dietary n-6 fatty acids from seed oils (sunflower, safflower, peanut, canola), which leaves us at risk for chronic inflammation, atherosclerosis and cardiovascular disease.

By increasing our intake of n-3 polyunsaturated fatty acids, either through diet or supplementation, and/or by decreasing n-6 fatty acid consumption, we can rebalance the inflammatory response and reduce our risk of cardiovascular and other inflammatory diseases.

Sources:

Danaei G, Ding EL, Mozaffarian D et al. The preventable causes of death in the United States: Comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Medicine April 2009;6(4)
http://dx.doi.org/10.1371/journal.pmed.1000058
Kris-Etherton PPM, Harris WS, Appel LJ. Fish consumption, fils oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 2003;23:e20-e30.
http://dx.doi.org/10.1161/01.ATV.0000038493.65177.94
Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC. Effect of different antilipidemic agents and diets on mortality. A systematic review. Arch Intern Med 2005;165:725-730.
http://archinte.ama-assn.org/cgi/reprint/165/7/725

Omega-3 fatty acid deficiency causes premature deaths

2009-07-11T04:50:00Z

"Omega-3 deficiency causes 96,000 US deaths per year, say researchers". That was the headline of a recent NutraIngredients article (1). The title highlights one of the more surprising finding of a study on "The preventable causes of death in the United States: Comparative risk assessment of dietary, lifestyle, and metabolic risk factors" (2).

A group of researchers set out to identify the lifestyle, dietary and metabolic health risk factors responsible for the greatest number of premature and preventable deaths in the United States. Metabolic risk factors are physiological indicators like blood pressure, glucose levels, LDL-cholesterol, etc. For any given risk factor to be included in their analysis, a number of conditions had to be met:

it had to be a known cause of disease-specific mortality,
a quantitative relationship between magnitude of risk and likelihood of death from a specific disease had to be available from observational or controlled studies,
the risk factor had to be controllable through lifestyle changes or medical intervention, and
representative risk factor distribution data for the general population had to be available.

If one knows the distribution of a given risk factor in the general population, and if the relation between its magnitude and the probability of disease-specific death from that risk factor can be quantified, then one can estimate the proportional reduction in the number of deaths that could be achieved by eliminating that risk factor. With this information it is then a simple matter to estimate the actual number of premature deaths that could be avoided by eliminating that risk factor; it is the product of the proportional reduction in the number of deaths and the actual number of deaths from that disease.

Here are the author′s estimates (2) for the number of deaths that could have been prevented in the U.S. in 2005, if the following twelve risk factors had been eliminated (confidence intervals in parentheses):

smoking 467,000 (436,000 - 500,000)
high blood pressure 395,000 (372,000 - 414,000)
overweight-obesity 216,000 (188,000 - 237,000)
physical inactivity 191,000 (164,000 - 222,000)
high blood glucose 190,000 (163,000 - 217,000)
high LDL-cholesterol 113,000 (94,000 - 124,000)
high dietary sodium 102,000 (97,000 - 107,000)
low dietary omega-3 fatty acids from seafood 84,000 (72,000 - 96,000)
high dietary trans fatty acids 82,000 (63,000 - 97,000)
excessive alcohol use 64,000 (51,000 - 69,000)
low intake of fruits and vegetables 58,000 (44,000 - 74,000)
low dietary polyunsaturated fatty acids (PUFAs) 15,000 (11,000 - 20,000)

Not surprisingly, smoking and high blood pressure were found to be by far the most serious risk factors for premature death. The high health risk posed by obesity, physical inactivity and high blood glucose had to be expected as well. The most surprising finding, though, has to be the importance of omega-3 fatty acids from fish. A lack of EPA and DHA in the diet turned out to be nearly as large a risk factor as high LDL-cholesterol or sodium levels, and more of a risk than trans fatty acids and low intakes of fruits and vegetables.

Some of the variables in this list seem like strange choices. For example, blood pressure and sodium intake aren′t independent of one another; increased sodium intake increases blood pressure. Similarly, there has to be a connection between overweight-obesity and physical inactivity. On the other hand, a number of well-known risk factors — caloric intake, triglyceride and HDL-cholesterol levels — were excluded, because their causal connections to specific diseases are less well established. Vitamin D is another surprising omission.

Be that as it may, these considerations are unlikely to put the omega-3 results in question. So, if you don′t like fish, supplement with EPA/DHA. It′s one of the most affordable and effective health measures you can take.

Sources:

Shane Starling. Omega-3 deficiency causes 96,000 US deaths per year, say researchers. NutraIngredients June 26, 2009.
http://www.nutraingredients-usa.com/content/view/print/252050
Danaei G, Ding EL, Mozaffarian D et al. The preventable causes of death in the United States: Comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Medicine April 2009;6(4).
http://dx.doi.org/10.1371/journal.pmed.1000058